噻托溴铵对烟雾吸入性损伤大鼠肺的保护作用

发布时间：2018-11-18 13:11

【摘要】：目的吸入性损伤是烧伤患者的头号杀手,具有很高的发生率和死亡率。它会导致气道梗阻、肺不张或肺萎陷,最终造成呼吸功能衰竭。噻托溴铵属于高选择性M1,M3受体长效拮抗药,目前广泛应用于COPD和哮喘稳定期治疗,用以扩张支气管,减少粘液分泌。它还对COPD气道炎症和重塑具有抑制作用。本实验以烟雾吸入性损伤大鼠为模型,通过研究雾化吸入噻托溴铵后大鼠肺组织的病理变化、炎症反应以及氧化反应的变化,来探讨噻托溴铵对烟雾吸入性损伤后肺的保护作用。方法将42只健康雄性SD大鼠随机分成3组：假伤组(n=10,未损伤),治疗组(n=16,伤后予噻托溴铵治疗),对照组(n=16,损伤未予噻托溴铵治疗),假伤组未予处理,对照组和治疗组建立烟雾吸入性损伤模型,伤后1小时开始,治疗组吸入噻托溴铵36微克(μg)/3ml生理盐水,对照组吸入3m1生理盐水,20分钟吸完,每8小时重复给药一次。于伤后24小时处死大鼠,腹主动脉取血,离心后测血清白介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α；剖胸取左肺,用10%甲醛固定,切片、染色后用光镜进行病理形态学观察；取右肺组织,用离心机制成匀浆,取上清液测髓过氧化物酶(MPO)、丙二醛(MDA)和超氧化物歧化酶(SOD)。对所得数据使用SPSS13.0统计软件进行处理,各组均数采用单因素ANOVA进行分析。结果1.一般情况观察：致伤后大鼠出现精神萎靡,呼吸、心率加快的症状,将大鼠放在空旷区休息10分钟,上述症状逐渐改善。 2.肺组织大体及光学显微镜观察：假伤组大鼠肺组织呈粉红色,无充血、水肿及出血。对照组可见充血、水肿,散在斑点状出血,治疗组充血、水肿及出血较对照组减轻。H.E染色显示,假伤组肺泡腔清晰,结构完整,肺泡壁光滑,间隔均匀一致,肺泡腔中无渗液及炎性细胞。损伤后肺组织明显水肿、渗出及出血,肺泡组织破坏,出现局灶性肺不张及肺萎陷,肺泡壁明显增厚,肺泡腔内可见粘液分泌及炎细胞渗出。噻托溴铵治疗组肺组织充血、水肿及出血有所减轻,肺泡壁稍有增厚,肺泡腔内粘液分泌及炎细胞渗出减少。 3.各组大鼠血清TNF-α,IL-6及IL-10的比较：对照组和治疗组血清TNF-α、IL-6、IL-10均高于假伤组(P0.01)。治疗组IL-6、TNF-α低于对照组(P0.01)IL-10高于对照组(P0.01)。 4.各组大鼠肺组织MPO、MDA、SOD的比较：对照组和治疗组肺匀浆MPO、MDA水平高于假伤组(P0.01),SOD水平低于假伤组(P0.01)。治疗组MDA、MPO均低于对照组(P0.01),SOD高于对照组(P0.01)。结论噻托溴铵可以减轻支气管梗阻,降低肺不张和(或)肺萎陷的发生率；可以抑制促炎因子IL-6、TNF-α的释放,促进抗炎因子IL-10的释放,减轻过度炎症反应对机体的损伤；还可以降低损伤后肺组织MPO, MDA水平,提高SOD活性,具有抗氧化的作用。因此,噻托溴铵对烟雾吸入性损伤大鼠肺具有保护作用。
[Abstract]:Objective inhalation injury is the leading killer of burn patients with high incidence and mortality. It can lead to obstruction of the airway, atelectasis or collapse of the lung, leading to respiratory failure. Tiotropium bromide is a long-acting antagonist of highly selective M _ (1) N _ (3) receptor. It is widely used in the treatment of COPD and asthma stable period to dilate bronchi and reduce mucus secretion. It also inhibits airway inflammation and remodeling in COPD. In this study, the pathological changes of lung tissue, the inflammatory reaction and the oxidative reaction of the rats after inhalation of tiotropium bromide were studied by using smoke inhalation injury as the model. To investigate the protective effect of tiotropium bromide on lung after smoke inhalation injury. Methods Forty-two healthy male SD rats were randomly divided into three groups: sham injury group (n = 10, no injury), treatment group (n = 16, treated with tiotropium bromide after injury), control group (n = 16, injury was not treated with tiotropium bromide), and sham injury group, without treatment. Smoke inhalation injury model was established in the control group and the treatment group. Starting from 1 hour after injury, the treatment group inhaled 36 渭 g (渭 g) / 3ml normal saline of tiotropium bromide, while the control group inhaled 3m1 saline for 20 minutes, and repeated administration every 8 hours. The rats were sacrificed 24 hours after injury, blood was taken from abdominal aorta, serum interleukin (IL)-6 and tumor necrosis factor (TNF)-伪 were measured after centrifugation. The left lung was dissected and fixed with 10% formaldehyde. The right lung tissue was taken and made into homogenate by centrifuge. The supernatant was used to measure (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD).) in supernatant. The data were processed by SPSS13.0 software, and the mean of each group was analyzed by single factor ANOVA. Result 1. General observation: after injury, the rats developed symptoms of mental retardation, respiration, and accelerated heart rate. The rats were placed in an open area for 10 minutes to rest, and the above symptoms gradually improved. 2. Gross and optical microscope observation of lung tissue: the pulmonary tissue of sham injury group was pink, without hyperemia, edema and haemorrhage. Hyperemia, edema and speckle hemorrhage were observed in the control group. The congestion, edema and bleeding in the treatment group were less than those in the control group. The alveolar cavity was clear, the structure was intact, the alveolar wall was smooth and the interval was uniform in the sham injury group. No exudate or inflammatory cells were found in the alveolar cavity. After injury, there were obvious edema, exudation and hemorrhage of lung tissue, destruction of alveolar tissue, focal atelectasis and collapse of lung, obvious thickening of alveolar wall, mucus secretion and inflammatory cell exudation in alveolar cavity. The hyperemia, edema and hemorrhage of lung tissue were alleviated, alveolar wall was slightly thickened, mucus secretion and inflammatory cell exudation were decreased in tiotropium treatment group. 3. Comparison of serum TNF- 伪, IL-6 and IL-10: serum TNF- 伪 and IL-6,IL-10 in control group and treatment group were higher than those in sham injury group (P0.01). The IL-6,TNF- 伪 in the treatment group was lower than that in the control group (P 0.01) and the IL-10 was higher in the treatment group than in the control group (P 0.01). 4. Comparison of MPO,MDA,SOD in lung tissue of rats in each group: the level of MPO,MDA in lung homogenate of control group and treatment group was higher than that of sham injury group (P0.01), SOD level was lower than that of sham injury group (P0.01). The MDA,MPO of the treatment group was lower than that of the control group (P0.01), SOD was higher than that of the control group (P0.01). Conclusion Tiotropium bromide can relieve bronchial obstruction and reduce the incidence of atelectasis and / or pulmonary collapse. It can inhibit the release of pro-inflammatory factor IL-6,TNF- 伪, promote the release of anti-inflammatory factor IL-10, and alleviate the damage caused by excessive inflammatory reaction. It can also reduce the level of MPO, MDA and increase the activity of SOD after injury. Therefore, tiotropium bromide has protective effect on lung injury induced by smoke inhalation in rats.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R644

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